Orthotopic mouse lung transplantation as experimental methodology to study transplant and tumor biology

Abstract

Unlike other solid organs, vascularized mouse lung transplantation has only recently been developed. In this publication we describe the detailed method for performing a vascularized and aerated mouse orthotopic lung transplant, which to date represents the most physiologic mouse model of lung transplantation. The procedure is divided into two separate portions consisting of donor harvest followed by implantation using the cuff technique for bronchovascular anastomoses. After a several month training period the procedure can be successfully mastered and in experienced hands requires approximately 90 minutes to perform. After an initial learning curve perioperative survival is close to 100%. As over time the donor hematopoietic cells in the transplanted lung are replaced by those of the host, thereby creating a “chimeric lung”, this model represents a novel research tool for the study of transplantation biology as well as other disease processes such as malignancies.

In vivo two-photon imaging reveals monocyte-dependent neutrophil extravasation during pulmonary inflammation

“…After 18-h storage in low-potassium dextran glucose at 4°C, left BALB/c lungs were transplanted orthotopically into LysM-GFP mice as described (20,36). Two-Photon Microscopy.…”

Models of Lung Transplant Research: a consensus statement from the National Heart, Lung, and Blood Institute workshop

“…The advancement of surgical techniques to accomplish single-lung transplantation in mice has permitted access to resources such as transgenic mice that can facilitate cellular tracking and pathway targeting (33,114,115). However, while the AR model was again easily established by using MHC-mismatched mice, developing a robust model of OB has been more challenging.…”

Emergency granulopoiesis promotes neutrophil-dendritic cell encounters that prevent mouse lung allograft acceptance

“…10,11 Recipients were treated with MR1 (250 g on day 0) and CTLA4-Ig (200 g on day 2; Bio-X-Cell). 12 Neutrophils were depleted through IV injection of Ly6G-specific Abs (1A8; 250 g; Bio-X-Cell) 4 hours before surgery, as described previously.…”